Pancreatic Neuroendocrine Tumors (PanNETs) are the second most common malignancy of the pancreas. The ten-year survival rate is only 40% (1-3). They are usually sporadic, but they can arise in multiple endocrine neoplasia type 1 and more rarely in other syndromes, including von Hippel-Lindau (VHL) syndrome and tuberous sclerosis (4). “Functional” PanNETs secrete hormones that cause systemic effects, while “Nonfunctional” PanNETs do not and therefore cannot always be readily distinguished from other neoplasms of the pancreas. Non-functional PanNETs grow silently and patients may present with either an asymptomatic abdominal mass or symptoms of abdominal pain secondary to compression by a large tumor. Surgical resection is the treatment of choice, but many patients present with unresectable tumors or extensive metastatic disease, and medical therapies are relatively ineffective.
There is currently insufficient information about this tumor to either predict prognosis of patients diagnosed with PanNETs or to develop companion diagnostics and personalized treatments to improve disease management. Biallelic inactivation of the MEN1 gene, usually by a mutation in one allele coupled with loss of the remaining wild-type allele, occurs in 25-30% of PanNETs (5, 6). Chromosomal gains and losses, and expression analyses, have identified candidate loci for genes involved in the development of PanNETs, but these have not been substantiated by genetic or functional analyses (7-9).
There is a continuing need in the art to identify appropriate therapies and to predict outcome of patients with pancreatic tumors.